The aim of this prospective study is to examine the relation of physical activity (PA) and cardiorespiratory fitness (CRF) to health in the middle and later years of life. Health is broadly defined here and encompasses measures of cause-specific and all-cause mortality, disease morbidity, and functional health status. The study population includes 14,383 women and 46,278 men who have been, or will be, examined at least once at a preventive medicine clinic from 1970 to 2002. Follow-up for mortality will include 216,356 woman-years and 735,554 man-years of observation, expected to yield 436 deaths in women and 3,276 deaths in men. An important strength of the study is that there is an objective measure of CRF from a maximal exercise test for each individual in this cohort. The database also includes demographic, behavioral, and clinical data from the examination, health habit and health status measurements from mail surveys, and information on vital status. The objective fitness and clinical data offer advantages over studies in which only self-reports of PA and clinical status are available, and this database allows us to control for baseline health status and numerous demographic, behavioral, health history, and clinical variables. We will expand the database by extending mortality follow-up for 4 years and by conducting an additional mail survey to identify nonfatal endpoints. This will allow us to address several issues. Although there is general agreement that regular exercise contributes to good health and function, several details need further evaluation to refine public health and clinical recommendations for PA. Issues we propose to investigate during the next grant period are 1) the specific role of exercise intensity with respect to health and function, 2) the shape of the CRF and health dose-response curve, 3) the importance of fitness in women's health and in the health and function of both men and women >60 years of age, 4) the role of low fitness in the development of specific diseases - notably site-specific cancers and stroke, and 5) how diet might modify the relation between fitness and health. The first 2 of these topics remain controversial, there are only limited data on issues 3 and 4, and there are essentially no data regarding issue. Our cohort is the largest prospective study of women with maximal exercise test results. This will allow us to assess the relation between fitness and cause-specific morbidity and mortality, as well as the effect of change in fitness on women's health. We expect 10,600 woman-years and 37,988 man-years of follow-up in persons >60 years of age, making this cohort increasingly valuable as a resource for evaluating the role of PA and CRF in the preservation of health and function and the promotion of a high quality of life as people age. Continuation of this study has the potential to make important additional contributions to our understanding of the health benefits of a fit and active way of life.